Malignant tumors in vagal-innervated organs: Exploring its homeostatic role

Abstract

Cancer remains a significant global health challenge, with its progression shaped by complex and multifactorial mechanisms. Recent research suggests that the vagus nerve could play a critical role in mediating communication between the tumor microenvironment and the central nervous system (CNS). This review highlights the diversity of vagal afferent receptors, which could position the vagus nerve as a unique pathway for transmitting immune, metabolic, mechanical, and chemical signals from tumors to the CNS. Such signaling could influence systemic disease progression and tumor-related responses. Additionally, the vagus nerve's interactions with the microbiome and the renin-angiotensin system (RAS)—both implicated in cancer biology—further underscore its potential central role in modulating tumor-related processes. Contradictions in the literature, particularly concerning vagal fibers, illustrate the complexity of its involvement in tumor progression, with both tumor-promoting and tumor-suppressive effects reported depending on cancer type and context. These contradictions often overlook certain experimental biases, such as the failure to distinguish between vagal afferent and efferent fibers during vagotomies or the localized parasympathetic effects that cannot always be extrapolated to the systemic level. By focusing on the homeostatic role of the vagus nerve, understanding these mechanisms could open the door to new perspectives in cancer research related to the vagus nerve and lead to potential therapeutic innovations.